The present invention relates generally to medical devices and methods and more particularly to a device and method for harvesting a quantity of transplantable corneal tissue along with adjacent, stem-cell-containing scleral tissue.
The anterior portion of the human eye normally contains corneal, limbal, and conjunctival epithelial tissue. Along with a film of tears, these tissues cover and protect the eye. The limbus is the marginal region of the cornea of the eye by which the cornea is continuous with the sclera. There is experimental and clinical evidence that limbal epithelial stem cells are located in the limbal area, presumably in the basal epithelium allowing the cells to be harvested as a lamellar eye tissue section. These dynamic cells maintain the corneal epithelial cell population and thus, the corneal surface integrity. Thus, the presence of functioning limbal stem cells is critical to the health and functioning of the eye. In the event the limbal stem cells become damaged or depleted, chronic inflammation, cloudy vision, and even blindness may result.
Damage or depletion to the limbal epithelial (stem) cells can result from a number of causes, including trauma, chemical or thermal burns, a disorder known as Stevens-Johnson syndrome, improper fitting or improper use of contact lenses, infections and/or scarring due to prior surgical procedures. In some cases, severe damage may lead to complete loss of the limbal epithelial cells.
In cases where only one eye is affected, the deficiency of limbal stem cells in the damaged eye may be treated by transplantation of a quantity of autologus limbal tissue harvested from the patient""s own contralateral healthy eye. However, because of the large amount of limbal tissue must be taken, it is not always possible to harvest enough limbal tissue from the patient""s good eye to complete the autologus transplant procedure in the bad eye. Also, the removal of tissue from the good eye can result in complications or visual changes in the good eye.
Another approach is to harvest limbal tissue (containing the limbal stem cells) from the eye of a cadaveric donor and to subsequently transplant those donor stem cells into the patient""s eye. The harvesting of limbal stem cells from cadaveric donors has heretofore typically been carried out by first removing the ocular globe from the donor""s body, then carefully removing a quantity of corneal tissue along with the scleral rim (the pericorneal scleral tissue) to obtain a generally disc shaped graft that includes the anterior cornea and adjacent limbus. This procedure has been performed by hand, and thus there is significant variability in the size and shape of the harvested graft.
The first studies proposing a pericorneal network responsible for the corneal epithelial cell maintenance were published three decades ago (Davanger M et al, 1971). Several authors have supported the hypothesis of a limbal stem cell system, based on the indirect evidence obtained from clinical experience and experimental work (Cotsarelis G et al, 1989; Lehrer M S et al, 1989; Chen J J et al, 1990; Dua H S et al, 1990; Dua H S et al, 2000). Epithelial cell behavior has also been extensively studied to evaluate the dynamics of its mitosis and migration (Thoft R A et al, 1983; Beebe D C et al, 1996). In cases of severe stem cell deficiency, surgical intervention is required. Limbal stem cell transplantation was first reported in 1989 by Kenyon and Tseng (Kenyon K R et al, 1989).
Results for the autologous transplantation of the limbal area in severe ocular surface disorders have been promising (Basti S et al, 2000; Tsai R J et al, 2000). In addition, allograft transplantation of these cells has been attempted, especially when a healthy donor tissue is not available in the contralateral eye (Tsai R J et al, 1994; Coster D J et al, 1995; Tsubota K et al, 1999; Dua H S et al, 1999). That is, the posterior two thirds of the cornea is manually removed, as well as the central 7.5 or 8 mm. Thus this annulus contains the outer 3 to 4 mm of limbal epithelium. Conversely, if this margin is too generous, then much more antigenic tissue is being transferred than is required for a successful epithelial stem cell graft. Most surgeons, however, will err on the conservative side, and transfer too much rather than too little tissue. Initial results for the autologous transplantation of the limbal area in severe ocular surface disorders have been promising (Basti S et al, 2000; Tsai R J et al, 2000). In addition, allograft transplantation of these cells has been attempted, especially when a healthy donor tissue is not available in the contralateral eye (Tsai R J et al, 1994; Coster D J et al, 1995; Tsubota K et al, 1999; Dua H S et al, 1999). With the development of new strategies for immunosupression and the refinements in screening for donor tissue compatibility, these allograft procedures for limbal stem cell transplantation have become more successful and thus been more common in the last few years (Terry M A, 2000; Shimazaki J et al, 2000; Shimazaki J et al, 1999; Tsai R J et al, 1994, Tsubota K, 1999).
The most troublesome technical concern with the transplantation procedure is the manual limbal tissue harvest. This is a time consuming process and certainly inaccurate, since the cut depth can only be visually estimated. In addition, the free-hand donor harvest of the limbal area is laborious, likely results in mechanical trauma and dehydration effects on vulnerable cell populations, and may be associated with poor preservation of the stem cells.
What is needed is a system to perform a superficial cut of the corneal-scleral surface to obtain a partial thickness lenticule containing a rim of sclera. This may ensure the presence of sufficient limbal area for 360xc2x0 to obtain the stem cells required for a successful transplant.
The present invention provides a system for harvesting corneal tissue along with adjacent scleral tissue containing limbal stem cells. The system of the present invention generally comprises an eye-contacting guide apparatus in combination with a tissue cutting apparatus. The eye-contacting guide apparatus may comprise a ring member or other suitable device that is positionable an the anterior surface of an eye which will guide the tissue cutting apparatus so as to form a precisely positioned cut in the eye tissue, harvesting the corneal and adjacent scleral tissue in which the limbal stem cells are located.
In accordance with the invention there is provided a system and method for harvesting, from a mammalian eye, a transplantable graft consisting of a quantity of corneal tissue along with a quantity of pericorneal tissue (e.g., scleral tissue) wherein the limbal stem cells are located. Generally, the system of the present invention comprises two components, namely a) an eye-contacting ring and guide member and b) a cutter. The eye-contacting ring and guide member may comprise a ring member, having an upper surface and a lower surface, and a cutter guide attached to or formed on the ring member for guiding the cutter along a predetermined path above the ring member. The cutter may generally comprise a handpiece attached to a blade for cutting the corneal and adjacent scleral tissue. The ring member may be sized such that when its lower surface is placed in contact with the anterior aspect of the eye, a portion of the cornea and adjacent scleral tissue will protrude upwardly through the ring member above the ring member""s upper surface and in relation to the cutter guide such that when the cutter is advanced along the cutter guide it will remove a disc shaped graft or xe2x80x9clenticulexe2x80x9d consisting of corneal tissue along with the desired quantity of adjacent scleral tissue wherein limbal stem cells are contained.
Still further in accordance with the present invention, a device of the invention may include a blade oscillator for causing the blade to oscillate or move from side to side to enhance its ability to form a clean cut through the corneal and scleral tissue. In some embodiments the oscillator is pneumatic.
Still further in accordance with the present invention, the ring member may be secured to the eye. In one embodiment, the ring member is secured to the eye by a partial vacuum. The partial vacuum may be contained within an anular structure which is made up of two surfaces, an upper surface and a lower surface, of the ring member and the surface of the eye.
Still further in accordance with the present invention, the inner diameter of the ring member may be about 14 mm to about 30 mm or about 14 mm to about 24 mm or about 14 mm to about 18 mm or about 16 mm or 16 mm.
Still further in accordance with the present invention, the cutter may include a guide-engaging member, which engages and interacts with the guide (e.g., guide member(s), guide trace, mechanical linkage, magnets or any other suitable apparatus for holding and guiding the cutter) located on the eye-contacting ring and guide apparatus.
Still further in accordance with the present invention, the ring member may include a handle useable for holding and manipulating the eye-contacting ring and guide apparatus.
Still further in accordance with the present invention, there are provided methods for harvesting a graft or lenticule consisting of corneal tissue and a quantity of pericorneal tissue and/or scleral tissue wherein limbal stem cells are located. In these methods a portion of the eye-contacting ring and guide member, for example, a lower surface of the ring member, may be placed in contact with the anterior aspect of the donor eye such that the cornea and a portion of the pericornial sclera protrudes upwardly through the ring member. The cutter may be engaged with the cutter guide and the cutter advanced along the cutter guide such that the blade means severs a quantity of corneal tissue along with a quantity of pericorneal scleral tissue.
Any and all features described herein and combinations of such features are included within the scope of the invention provided that such features of any such combination are not mutually exclusive.
These and other aspects and advantages of the present invention are apparent in the following detailed description and claims.